Several studies have demonstrated that thyroid hormone T3 promotes cancer cell growth, even though the molecular mechanism involved in such processes still needs to be elucidated. In this study we demonstrated that T3 induced proliferation in papillary thyroid carcinoma cell lines concomitantly with an up-regulation of cyclin D1 expression, that is a critical mitogen-regulated cell-cycle control element. Our data revealed that T3 enhanced the recruitment of the TRβ1/Oct-1 complex on Octamer-transcription factor-1 site within cyclin D1 promoter, leading to its transactivation. In addition, silencing of TRβ1 or Oct-1 expression by RNA interference reversed both increased cell proliferation and up-regulation of cyclin D1, underlying the important role of both transcriptional factors in mediating these effects. Finally, T3-induced increase in cell growth was abrogated after knocking down cyclin D1 expression. All these findings highlight a new molecular mechanism by which T3 promotes thyroid cancer cell growth.

T3 enhances thyroid cancer cell proliferation through TRβ1/Oct-1-mediated cyclin D1 activation

Perri, Anna;
2014-01-01

Abstract

Several studies have demonstrated that thyroid hormone T3 promotes cancer cell growth, even though the molecular mechanism involved in such processes still needs to be elucidated. In this study we demonstrated that T3 induced proliferation in papillary thyroid carcinoma cell lines concomitantly with an up-regulation of cyclin D1 expression, that is a critical mitogen-regulated cell-cycle control element. Our data revealed that T3 enhanced the recruitment of the TRβ1/Oct-1 complex on Octamer-transcription factor-1 site within cyclin D1 promoter, leading to its transactivation. In addition, silencing of TRβ1 or Oct-1 expression by RNA interference reversed both increased cell proliferation and up-regulation of cyclin D1, underlying the important role of both transcriptional factors in mediating these effects. Finally, T3-induced increase in cell growth was abrogated after knocking down cyclin D1 expression. All these findings highlight a new molecular mechanism by which T3 promotes thyroid cancer cell growth.
CycD1
Oct-1
Octamer-transcription factor-1
T3
TH
TRs
TRβ1
Thyroid cancer
Thyroid hormone receptor β1
cyclin D1
thyroid hormone
thyroid hormone receptor β1
thyroid hormone receptors
Carcinoma
Carcinoma, Papillary
Cell Line, Tumor
Cell Proliferation
Cyclin D1
Enzyme Activation
Gene Expression Regulation, Neoplastic
Humans
Models, Biological
Octamer Transcription Factor-1
Promoter Regions, Genetic
Proto-Oncogene Proteins c-akt
Thyroid Cancer, Papillary
Thyroid Hormone Receptors beta
Thyroid Neoplasms
Triiodothyronine
Up-Regulation
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11770/337364
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